Document 0036
 DOCN  M9460036
 TI    In vitro evolution of a neutralizing human antibody to human
       immunodeficiency virus type 1 to enhance affinity and broaden strain
       cross-reactivity.
 DT    9408
 AU    Barbas CF 3rd; Hu D; Dunlop N; Sawyer L; Cababa D; Hendry RM; Nara PL;
       Burton DR; Department of Molecular Biology, Scripps Research Institute,
       La; Jolla, CA 92037.
 SO    Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3809-13. Unique Identifier :
       AIDSLINE MED/94224831
 AB    A method is described that allows for the improvement of antibody
       affinity. This method, termed complementary-determining region (CDR)
       walking, does not require structural information on either antibody or
       antigen. Complementary-determining regions are targeted for random
       mutagenesis followed by selection for fitness, in this case increased
       binding affinity, by the phage-display approach. The current study
       targets a human CD4-binding-site anti-gp120 antibody that is potently
       and broadly neutralizing. Evolution of affinity of this antibody
       demonstrates in this case that affinity can be increased while
       reactivity to variants of human immunodeficiency virus type 1 is
       broadened. The neutralizing ability of this antibody is improved, as
       assayed with laboratory and primary clinical isolates of human
       immunodeficiency virus type 1. The ability to produce human antibodies
       of exceptional affinity and broad neutralizing ability has implications
       for the therapeutic and prophylactic application of antibodies for human
       immunodeficiency virus type 1 infection.
 DE    Amino Acid Sequence  Antibody Affinity  Base Sequence  Binding Sites
       Binding Sites, Antibody  Cross Reactions  Human  HIV
       Antibodies/GENETICS/*IMMUNOLOGY  HIV Antigens/*IMMUNOLOGY  HIV Envelope
       Protein gp120/*IMMUNOLOGY  HIV-1/*IMMUNOLOGY  In Vitro  Molecular
       Sequence Data  Mutagenesis, Site-Directed  Neutralization Tests
       Structure-Activity Relationship  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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